Gestodene (17.alpha.-ethynyl-17.beta.-hydroxy-18-methyl-4,15-estradien-3-one) of formula I ##STR5## is a highly efficacious gestagen usable, for example, in contraceptive preparations; as is well known in the art and disclosed in "Wiener klinische Wochenschrift" 93 (1981) 601-604 which disclosure is incorporated by reference herein.
Several methods for the preparation of gestodene are known. In each case, the compound is produced by ethynylation of a 17-ketone.
German Pat. No. 2,546,062 discloses ethynylations on 17-ketones of the following general Formula III: ##STR6## wherein Y is a free keto group or preferably a keto group blocked as a ketal, and one of the bonds in the 4,5-, 5,6- or 5,10-position means a carbon-carbon double bond and the other bonds mean respectively one carbon-carbon single bond, and A-B means a carbon-carbon double bond or the grouping ##STR7## wherein R' represents a hydrogen atom, a silyl, acyl, sulfonyl or nitro group.
By treating 18-methyl-4,15-estradiene-3,17-dione (Formula III: Y=O, A-B=CH.dbd.CH) with lithium acetylide, gestodene is obtained in a high yield of about 75%. However, this method is usable only for amounts of starting material compounds up to 100 g; ethynylation in this manner therefore cannot be performed on an industrial scale. Moreover, it has been found that the 18-methyl-4,15-estradiene-3,17-dione starting material can have a sensitizing effect in case of skin contact, consequently protective measures must be observed when handling 18-methyl-4,15-estradiene-3,17-dione.
Preparation of gastodene by way of the 3-ketals (Formula III: Y=ethylenedioxy or 2,2-dimethyl-1,3-propylenedioxy) has the drawback that the 3-ketals are obtained as mixtures of isomers in an oily form which can be purified only by chromatography.
German Pat. No. 2,749,104 which disclosure is incorporated by reference herein describes ethynylation on 17-ketones wherein the 3-keto group is blocked with 1,2-ethanedithiol (Formula III: Y=ethylene-dithio with a carbon-carbon double bond in the 4,5-position). Ethanedithiol constitutes a pollutant, even in small amounts, on account of its unpleasant odor. Furthermore, use of the thioketal blocking group is disadvantageous in that it can be split off after ethynylation only with a large excess of methyl iodide, an expensive reagent. Thus, any advantages of the thioketals such as ready crystallizability and almost quantitative conversion capability are outweighed.